Most of the immunosuppressive effects of interleukin‐10 (IL‐10) are related to functional inhibition of antigen‐presenting cells (APC). Herein, we investigate the influence of recombinant (r)IL‐10 on human dendritic cells (DC) purified from peripheral blood of healthy volunteers. First, we found that rIL‐10 inhibited in a dose‐dependent manner the proliferative responses as well as the production of IL‐2 and interferon‐γ (IFN‐γ) in mixed lymphocyte reaction (MLR) between purified T cells and DC. This rIL‐10 effect could be attributed to a direct effect on DC, as DC preincubated with rIL‐10 were found to be deficient in the induction of alloreactive T cells even when anti‐IL‐10 neutralizing mAb was added at the time of MLR. Flow cytometric analysis indicated that rIL‐10 did not modify the expression of ICAM‐1 (CD54) and B7‐1 (CD80), but decreased HLA‐DR and B7‐2 (CD86) expression at the DC surface. We conclude that the inhibitory effect of rIL‐10 on primary alloreactive T cell responses involves down‐regulation of class II MHC and B7‐2 expression at the DC surface.